Exploring the Antiproliferative Potency of Pyrido[2,3‐d]Pyrimidine Derivatives: Studies on Design, Synthesis, Anticancer Evaluation, SAR, Docking, and DFT Calculations DOI

Eman Abd‐Alsalam,

Hend N. Hafez,

M. G. Assay

и другие.

Chemistry & Biodiversity, Год журнала: 2023, Номер 21(2)

Опубликована: Дек. 12, 2023

Abstract Herein, an efficient method for the synthesis of a new series pyrido[2,3‐ d ]pyrimidine derivatives has been adopted through reaction hydrazinyl ] pyrimidine derivative ( 1 ) with different electrophilic species, such as ethyl cyanoacetate and 1,3 diketone derivatives, gave corresponding 2 – 5 ). Meanwhile, ][1,2,4]triazolo[4,3‐ ]pyrimidines 6 11 were synthesized via hydrazine phenylisothiocyanate, potassium thiocyanate, carbon disulfide. Compound was also submitted to react carbonyl compounds afford pyrido‐pyrimidine 12 15 All newly tested in vitro their antiproliferative activities against HCT‐116 MCF‐7 cell lines. Compounds , 3 7 8 displayed very strong inhibitory activity two lines compared standard drug doxorubicin. Furthermore, docking study most active performed thymidylate synthase enzyme (PDB: Code 6qxg). Moreover, DFT calculation carried out biologically reference (Doxorubicin) using B3LYP/6‐31G+(d,p) level theory. The calculated E HOMO LUMO energies used calculate global reactivity parameters. Finally, Molecular electrostatic potential (MEP) structure relationship (SAR) studied correlate relation between chemical reactivity.

Язык: Английский

A novel class of pyrazole analogues as aurora kinase A inhibitor: design, synthesis, and anticancer evaluation DOI

Digambar Yevale,

Nishith Teraiya,

Twinkle Lalwani

и другие.

Bioorganic Chemistry, Год журнала: 2023, Номер 141, С. 106901 - 106901

Опубликована: Окт. 1, 2023

Язык: Английский

Процитировано

11
Antiangiogenic potential of phytochemicals from Clerodendrum inerme (L.) Gaertn investigated through in silico and quantum computational methods DOI

Nusrath Yasmeen,

Anis Ahmad Chaudhary,

Salauddin Khan

и другие.

Molecular Diversity, Год журнала: 2024, Номер 29(1), С. 215 - 239

Опубликована: Апрель 28, 2024

Язык: Английский

Процитировано

4
Synthesis, crystal structure, and antiviral evaluation of new imidazopyridine-schiff base derivatives: in vitro and in silico anti-HIV studies DOI Creative Commons
Mohamed Azzouzi,

Abderrahim Ait Ouchaoui,

Omar Azougagh

и другие.

RSC Advances, Год журнала: 2024, Номер 14(50), С. 36902 - 36918

Опубликована: Янв. 1, 2024

Imidazo[1,2- a ]pyridine-Schiff base derivatives were synthesized, characterized, and evaluated for their anti-HIV potential. Molecular docking ADME performed discussed.

Язык: Английский

Процитировано

3
TiO2 Nanoparticles Catalyzed Synthesis, Pharmacological Evaluation, and Molecular Docking Studies of New Pyrido[2,3-d]Pyrimidine Derivatives as CDK1 Inhibitors DOI

Eman Abd Alsalam,

Hanem M. Awad, Eslam M. Abbass

и другие.

Chemistry Africa, Год журнала: 2025, Номер unknown

Опубликована: Март 9, 2025

Язык: Английский

Процитировано

0
Copper(I) hydrazonate complexes as efficient catalysts for synthesizing substituted pyrimidines via acceptorless dehydrogenative coupling of amidine and alcohols DOI

Sekar Sandhiya,

K. Radhakrishna,

Jayakumar Megapriya

и другие.

Inorganica Chimica Acta, Год журнала: 2025, Номер unknown, С. 122678 - 122678

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
In Silico Identification of Putative Allosteric Pockets and Inhibitors for the KRASG13D-SOS1 Complex in Cancer Therapy DOI Open Access
Zehra Sarica, Özge Kürkçüoğlu, Fethiye Aylin Sungur

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3293 - 3293

Опубликована: Апрель 2, 2025

RAS mutations occur in about 30% of human cancers, leading to enhanced signaling and tumor growth. KRAS is the most commonly mutated oncogene tumors, especially lung, pancreatic, colorectal cancers. Direct targeting difficult due its highly conserved sequence; but, complex with guanine nucleotide exchange factor Son Sevenless (SOS) 1 promises an attractive target for inhibiting RAS-mediated signaling. Here, we first revealed putative allosteric binding sites SOS1, KRASG12C-SOS1 complex, ternary KRASG13D-SOS1 structures using two network-based models, essential site scanning analysis residue interaction network model. The results enabled us identify new pockets complex. These were then screened together known ligand against natural compounds InterBioScreen (IBS) database Glide software package developed by Schrödinger, Inc. docking poses seven hit assessed 400 ns long molecular dynamics (MD) simulations independent replicas Desmond, coupled thermal MM-GBSA calculations estimation free energy values. structural skeleton proposed consists different functional groups heterocyclic rings that possess anti-cancer activity exhibit persistent interactions key residues throughout MD simulations. STOCK1N-09823 was determined as promising promoted disruption R73 (chain A)/N879 A)/Y884, which are SOS1-mediated activation.

Язык: Английский

Процитировано

0
Rational design and eco-friendly one-pot multicomponent synthesis of novel ethylidenehydrazineylthiazol-4(5H)-ones as potential apoptotic inducers targeting wild and mutant EGFR-TK in triple negative breast cancer DOI
Eslam M. Abbass, Ahmed A. Al‐Karmalawy, Marwa Sharaky

и другие.

Bioorganic Chemistry, Год журнала: 2023, Номер 142, С. 106936 - 106936

Опубликована: Окт. 24, 2023

Язык: Английский

Процитировано

7
Design and Synthesis of Novel Pyrazolopyrimidine Candidates As Promising EGFR-T790M Inhibitors and Apoptosis Inducers DOI

Ahmed A. Abdel Gaber,

Marwa Sharaky, Ayman Abo Elmaaty

и другие.

Future Medicinal Chemistry, Год журнала: 2023, Номер 15(19), С. 1773 - 1790

Опубликована: Окт. 1, 2023

Aim: Our objective was to design and synthesize a new range of pyrazolopyrimidines while maintaining the key pharmacophoric features EGFR tyrosine kinase inhibitors. Materials & methods: Percentage inhibition in 14 human cancer cell lines IC50 values were recorded. Compounds 6c, 7e 7f examined against both wild mutant (T790M) subtypes. Apoptosis markers, cycle arrest, apoptosis assay molecular docking performed. Results: demonstrated superior inhibitory potentials A study showed that compounds 6c had best fit. Conclusion: The designed candidates potential as promising EGFR-T790M inhibitors agrees with proposed rationale.

Язык: Английский

Процитировано

7
Design, Synthesis, Drug-Likeness, anti-Inflammatory, Antimicrobial Activity, and Molecular Docking Studies of Pyrimidine Analogs DOI
N. Jeelan Basha,

K. T. Akshay

Polycyclic aromatic compounds, Год журнала: 2024, Номер unknown, С. 1 - 13

Опубликована: Апрель 1, 2024

Grounded on medicinal significances of pyrimidines, herein we are reporting initially the design and synthesis 1-(2-benzylthiopyrimidin-4-yl)-benzimidazol-2-thioacetic acid/thioacetate 2(a, b), 1-(2-benzylthiopyrimidin-4-yl)-3,5 diaryl-2-pyrazoline (3) 1-(2-benzylthiopyrimidin-4-yl)-3,5-dimethylpyrazole (4). In silico screening such as molecular docking studies these compounds with inflammation-causing enzyme cyclooxagenase-2 (COX-2) suggests that only 2a has shown a strong affinity for COX-2 (−9.0 kcal/mol) forms three hydrogen bonds active amino acid residues in comparison standard anti-inflammatory drugs celecoxib (-8.8 indomethacin (-7.7 kcal/mol). However, vitro, activity reveals IC50 compound was 3.5 μM compared to 0.65 μM. Also, displayed comparable antibacterial drug gentamycin against E. coli MIC 6.5 Furthermore, drug-likeness potent studied using Swiss ADME Mol inspiration software. All showed optimum without violating Lipinski's rule five. With our best observation based comparative SAR analogs indomethacin, conclude could develop therapeutically agent.

Язык: Английский

Процитировано

2
Structural and molecular insights from dual inhibitors of EGFR and VEGFR2 as a strategy to improve the efficacy of cancer therapy DOI
Krisyanti Budipramana, Frangky Sangande

Chemical Biology & Drug Design, Год журнала: 2024, Номер 103(5)

Опубликована: Май 1, 2024

Abstract Epidermal growth factor receptor (EGFR) and vascular endothelial 2 (VEGFR2) are known as valid targets for cancer therapy. Overexpression of EGFR induces uncontrolled cell proliferation VEGF expression triggering angiogenesis via VEGFR2 signaling. On the other hand, independent signaling is already one mechanisms resistance to anti‐EGFR Therefore, drugs that act dual inhibitors can be a solution problem drug increase effectiveness In this review, we summarize relationship between signal transduction in promoting how their kinase domain structures affect selectivity an inhibitor basis designing inhibitors. addition, several recent studies on development involving docking simulations were highlighted paper provide some references such pharmacophore features key residues further research, especially computer‐aided design.

Язык: Английский

Процитировано

2